Antibiotic Effects on the Developing Microbiome, Metabolome and Morbidities in Preterm Neonates
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 98
- 试验地点
- 1
- 主要终点
- Number of Events of Composite Morbidities and Mortality, Including Necrotizing Enterocolitis (NEC), Late Onset Sepsis (LOS), Bronchopulmonary Dysplasia (BPD) and Death
研究概览
简要总结
Prolonged antibiotic use in preterm neonates has significant consequences on the developing intestinal microbiome, metabolome and host response, predisposing the neonate to various major morbidities, including necrotizing enterocolitis (NEC), late-onset sepsis, bronchopulmonary dysplasia (BPD), and mortality.
The hypothesis is that early and prolonged antibiotic use in preterm neonates has significant consequences on the developing intestinal microbiome, metabolome and host response, predisposing the neonate to various major morbidities. It is possible that the effect of this widespread antibiotic use outweighs the potential benefits. This study will randomize preterm infants born at less than 33 weeks gestation to either pre-emptive antibiotics or no-pre-emptive antibiotics.
The purpose of this research is to evaluate the risks and benefits of current practice to determine optimal levels of antibiotic use that protects the babies from infection with minimal effect on the microbiome and subsequent adverse outcomes related to overuse of antibiotics.
详细描述
A majority of preterm very low birthweight (VLBW) infants are exposed to antibiotics. Surveys from large databases in the US show that the rate of culture proven bacteremia in these infants at birth is only between 1-2 percent.
Antibiotic use, especially when repeated, induces a perturbation ("dysbiosis") in gut microbiota that may not recover to the basal state. Antibiotic use increases the risk of subsequent disease and adverse outcomes. The dependence of the developing immune system on the intestinal microbiota is supported by emerging evidence from studies in animals demonstrating decreased resistance to subsequent disease with early exposure to antibiotics.
A retrospective review of 50,0261 neonates across 127 neonatal intensive care units (NICUs) from California showed a forty-fold variation in NICU antibiotic prescribing practice with similar burdens of proven infection and mortality. A large number of preterm infants are thus subjected to a potentially harmful course of antibiotics that provides no clear benefit. There remains a major gap in our understanding of antibiotic-related intestinal microbial dysbiosis and how this may result in disease.
There will be two aims. In the first aim, a prospective, randomized pilot study, will test the effects of pre-emptive postnatal antibiotics on the microbiome, metabolome and inflammatory responses in the neonate during the NICU course. The second aim will assess the effects of pre-emptive postnatal antibiotics on adverse outcomes in the neonate while in the NICU. The hypothesis is that higher antibiotic use will not be associated with decreased early onset sepsis and in fact, will be associated with increased adverse outcomes including retinopathy of prematurity, necrotizing enterocolitis, spontaneous ileal perforation, late onset sepsis, chronic lung disease, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, and mortality.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 23 Weeks 至 33 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All infants less than 33 weeks gestation.
排除标准
- •Infants who are non-viable at birth.
研究组 & 干预措施
Group A - Antibiotics Indicated
These neonates have a clinical indication to receive antibiotics such as symptoms out of expected for gestation OR delivered to moms with high perinatal infectious risks.
The standard of care antibiotics include Ampicillin and Gentamicin or Cefotaxime.
Study interventions will include the collection of samples for the following: breast milk, gastric fluid and stool samples for analysis of the microbiome.
干预措施: Antibiotic (Drug)
Group A - Antibiotics Indicated
These neonates have a clinical indication to receive antibiotics such as symptoms out of expected for gestation OR delivered to moms with high perinatal infectious risks.
The standard of care antibiotics include Ampicillin and Gentamicin or Cefotaxime.
Study interventions will include the collection of samples for the following: breast milk, gastric fluid and stool samples for analysis of the microbiome.
干预措施: Gastric fluid (Other)
Group A - Antibiotics Indicated
These neonates have a clinical indication to receive antibiotics such as symptoms out of expected for gestation OR delivered to moms with high perinatal infectious risks.
The standard of care antibiotics include Ampicillin and Gentamicin or Cefotaxime.
Study interventions will include the collection of samples for the following: breast milk, gastric fluid and stool samples for analysis of the microbiome.
干预措施: Breast milk (Other)
Group A - Antibiotics Indicated
These neonates have a clinical indication to receive antibiotics such as symptoms out of expected for gestation OR delivered to moms with high perinatal infectious risks.
The standard of care antibiotics include Ampicillin and Gentamicin or Cefotaxime.
Study interventions will include the collection of samples for the following: breast milk, gastric fluid and stool samples for analysis of the microbiome.
干预措施: Stool samples (Other)
Group B - antibiotics not indicated
These neonates are asymptomatic AND are delivered to moms with low perinatal infectious risk factors.
Antibiotics is not indicated for this group as standard of care.
Study interventions will include the collection of samples for the following: breast milk, gastric fluid and stool samples for analysis of the microbiome.
干预措施: Gastric fluid (Other)
Group B - antibiotics not indicated
These neonates are asymptomatic AND are delivered to moms with low perinatal infectious risk factors.
Antibiotics is not indicated for this group as standard of care.
Study interventions will include the collection of samples for the following: breast milk, gastric fluid and stool samples for analysis of the microbiome.
干预措施: Breast milk (Other)
Group B - antibiotics not indicated
These neonates are asymptomatic AND are delivered to moms with low perinatal infectious risk factors.
Antibiotics is not indicated for this group as standard of care.
Study interventions will include the collection of samples for the following: breast milk, gastric fluid and stool samples for analysis of the microbiome.
干预措施: Stool samples (Other)
Group CI/randomized to antibiotics
This group will be randomized to receive standard of care antibiotics which include Ampicillin and Gentamicin or Cefotaxime.
Study interventions will include the collection of samples for the following: breast milk, gastric fluid and stool samples for analysis of the microbiome.
干预措施: Gastric fluid (Other)
Group CI/randomized to antibiotics
This group will be randomized to receive standard of care antibiotics which include Ampicillin and Gentamicin or Cefotaxime.
Study interventions will include the collection of samples for the following: breast milk, gastric fluid and stool samples for analysis of the microbiome.
干预措施: Breast milk (Other)
Group CI/randomized to antibiotics
This group will be randomized to receive standard of care antibiotics which include Ampicillin and Gentamicin or Cefotaxime.
Study interventions will include the collection of samples for the following: breast milk, gastric fluid and stool samples for analysis of the microbiome.
干预措施: Stool samples (Other)
Group CI/randomized to antibiotics
This group will be randomized to receive standard of care antibiotics which include Ampicillin and Gentamicin or Cefotaxime.
Study interventions will include the collection of samples for the following: breast milk, gastric fluid and stool samples for analysis of the microbiome.
干预措施: Antibiotics (Drug)
Group CII/randomized to no antibiotics
This group will be randomized not to receive standard of care antibiotics.
Study interventions will include the collection of samples for the following: breast milk, gastric fluid and stool samples for analysis of the microbiome.
干预措施: Gastric fluid (Other)
Group CII/randomized to no antibiotics
This group will be randomized not to receive standard of care antibiotics.
Study interventions will include the collection of samples for the following: breast milk, gastric fluid and stool samples for analysis of the microbiome.
干预措施: Breast milk (Other)
Group CII/randomized to no antibiotics
This group will be randomized not to receive standard of care antibiotics.
Study interventions will include the collection of samples for the following: breast milk, gastric fluid and stool samples for analysis of the microbiome.
干预措施: Stool samples (Other)
结局指标
主要结局
Number of Events of Composite Morbidities and Mortality, Including Necrotizing Enterocolitis (NEC), Late Onset Sepsis (LOS), Bronchopulmonary Dysplasia (BPD) and Death
时间窗: Until discharge from the NICU, up to 1 year
Enrolled subjects' medical record will be reviewed to determine the number of patients with the composite outcome and the association between antibiotic administration and the components of the composite outcome
次要结局
- Number of Participants With Late Onset Sepsis(Until discharge from the NICU, up to 1 year)
- Number of Deaths(until discharge from the NICU, up to one year.)
- Number of Participants With Bronchopulmonary Dysplasia (BPD)(Until discharge from the NICU, up to 1 year)
- Number of Participants With Necrotizing Enterocolitis (NEC)(Until discharge from the NICU, up to 1 year)
- Length of Stay.(Average days +/- standard deviation of hospitalization, up to 15 weeks)